Vippagunta S R, Brittain H G, Grant D J
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455, USA.
Adv Drug Deliv Rev. 2001 May 16;48(1):3-26. doi: 10.1016/s0169-409x(01)00097-7.
Many drugs exist in the crystalline solid state due to reasons of stability and ease of handling during the various stages of drug development. Crystalline solids can exist in the form of polymorphs, solvates or hydrates. Phase transitions such as polymorph interconversion, desolvation of solvate, formation of hydrate and conversion of crystalline to amorphous form may occur during various pharmaceutical processes, which may alter the dissolution rate and transport characteristics of the drug. Hence it is desirable to choose the most suitable and stable form of the drug in the initial stages of drug development. The current focus of research in the solid-state area is to understand the origins of polymorphism at the molecular level, and to predict and prepare the most stable polymorph of a drug. The recent advances in computational tools allow the prediction of possible polymorphs of the drug from its molecular structure. Sensitive analytical methods are being developed to understand the nature of polymorphism and to characterize the various crystalline forms of a drug in its dosage form. The aim of this review is to emphasize the recent advances made in the area of prediction and characterization of polymorphs and solvates, to address the current challenges faced by pharmaceutical scientists and to anticipate future developments.
由于稳定性以及在药物研发各个阶段易于处理的原因，许多药物以结晶固态形式存在。结晶固体可以以多晶型物、溶剂化物或水合物的形式存在。在各种制药过程中可能会发生诸如多晶型物相互转化、溶剂化物去溶剂化、水合物形成以及结晶形式向无定形形式转化等相变，这可能会改变药物的溶解速率和转运特性。因此，在药物研发的初始阶段选择最合适和稳定的药物形式是很有必要的。固态领域当前的研究重点是在分子水平上理解多晶型现象的起源，并预测和制备药物最稳定的多晶型物。计算工具的最新进展使得能够从药物的分子结构预测其可能的多晶型物。正在开发灵敏的分析方法以了解多晶型现象的本质，并表征药物剂型中各种结晶形式。本综述的目的是强调在多晶型物和溶剂化物的预测与表征领域取得的最新进展，解决制药科学家目前面临的挑战，并展望未来的发展。
